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Non-small cell lung cancer (NSCLC) remains a significant global health burden, and there is an urgent need for new treatment options. Trophoblast cell surface antigen-2 (TROP-2), a target closely associated with NSCLC prognosis, has become a research hotspot in recent years. Notably, TROP-2-targeted antibody-drug conjugates (ADCs) have made groundbreaking advances in NSCLC therapy. Clinical studies have demonstrated that certain TROP-2 ADCs can significantly improve progression-free survival in previously treated patients with advanced or metastatic NSCLC, regardless of the presence of actionable genomic alterations. These agents have shown promising potential in both frontline and subsequent treatment settings. In terms of safety, while adverse effects affecting the hematologic, respiratory, and gastrointestinal systems are generally manageable, close clinical monitoring and timely management are still required. In conclusion, TROP-2 ADCs hold great promise in the treatment of NSCLC.